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CA2908697C - Targeted modification of rat genome - Google Patents

Targeted modification of rat genome Download PDF

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Publication number
CA2908697C
CA2908697C CA2908697A CA2908697A CA2908697C CA 2908697 C CA2908697 C CA 2908697C CA 2908697 A CA2908697 A CA 2908697A CA 2908697 A CA2908697 A CA 2908697A CA 2908697 C CA2908697 C CA 2908697C
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Canada
Prior art keywords
rat
nucleic acid
locus
acid sequence
cell
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Active
Application number
CA2908697A
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English (en)
French (fr)
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CA2908697A1 (en
Inventor
Jeffrey D. Lee
Alexander O. MUJICA
Wojtek Auerbach
Ka-Man Venus Lai
David M. Valenzuela
George D. Yancopoulos
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Regeneron Pharmaceuticals Inc
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Regeneron Pharmaceuticals Inc
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Publication of CA2908697A1 publication Critical patent/CA2908697A1/en
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    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027New or modified breeds of vertebrates
    • A01K67/0275Genetically modified vertebrates, e.g. transgenic
    • A01K67/0278Knock-in vertebrates, e.g. humanised vertebrates
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027New or modified breeds of vertebrates
    • A01K67/0275Genetically modified vertebrates, e.g. transgenic
    • A01K67/0276Knock-out vertebrates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61DVETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D19/00Instruments or methods for reproduction or fertilisation
    • A61D19/04Instruments or methods for reproduction or fertilisation for embryo transplantation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/715Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • C07K14/7155Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for interleukins [IL]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/775Apolipopeptides
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/87Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/90Stable introduction of foreign DNA into chromosome
    • C12N15/902Stable introduction of foreign DNA into chromosome using homologous recombination
    • C12N15/907Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00Genetically modified animals
    • A01K2217/07Animals genetically altered by homologous recombination
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00Animals characterised by species
    • A01K2227/10Mammal
    • A01K2227/105Murine
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00Animals characterised by purpose
    • A01K2267/03Animal model, e.g. for test or diseases
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00Animals characterised by purpose
    • A01K2267/03Animal model, e.g. for test or diseases
    • A01K2267/035Animal model for multifactorial diseases
    • A01K2267/0362Animal model for lipid/glucose metabolism, e.g. obesity, type-2 diabetes
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00Animals characterised by purpose
    • A01K2267/03Animal model, e.g. for test or diseases
    • A01K2267/035Animal model for multifactorial diseases
    • A01K2267/0381Animal model for diseases of the hematopoietic system
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • C12N2015/8527Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic for producing animal models, e.g. for tests or diseases
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2800/00Nucleic acids vectors
    • C12N2800/30Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2810/00Vectors comprising a targeting moiety

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Environmental Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Wood Science & Technology (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Animal Husbandry (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Toxicology (AREA)
  • Medicinal Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Mycology (AREA)
  • Immunology (AREA)
  • Public Health (AREA)
  • Reproductive Health (AREA)
  • Transplantation (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
CA2908697A 2013-04-16 2014-04-16 Targeted modification of rat genome Active CA2908697C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201361812319P 2013-04-16 2013-04-16
US61/812,319 2013-04-16
US201361914768P 2013-12-11 2013-12-11
US61/914,768 2013-12-11
PCT/US2014/034412 WO2014172489A2 (en) 2013-04-16 2014-04-16 Targeted modification of rat genome

Publications (2)

Publication Number Publication Date
CA2908697A1 CA2908697A1 (en) 2014-10-23
CA2908697C true CA2908697C (en) 2023-12-12

Family

ID=51687240

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2908697A Active CA2908697C (en) 2013-04-16 2014-04-16 Targeted modification of rat genome

Country Status (26)

Country Link
US (5) US20140310828A1 (pt)
EP (2) EP3456831B1 (pt)
JP (1) JP6411463B2 (pt)
KR (2) KR102186281B1 (pt)
CN (2) CN111500630A (pt)
AU (2) AU2014253942B9 (pt)
BR (1) BR112015026197B1 (pt)
CA (1) CA2908697C (pt)
CY (2) CY1120845T1 (pt)
DK (2) DK2986729T3 (pt)
ES (2) ES2888250T3 (pt)
HK (1) HK1214625A1 (pt)
HR (2) HRP20181648T1 (pt)
HU (2) HUE056903T2 (pt)
IL (2) IL241856B (pt)
LT (2) LT2986729T (pt)
MX (1) MX369747B (pt)
MY (1) MY177850A (pt)
PL (2) PL3456831T3 (pt)
PT (2) PT2986729T (pt)
RS (2) RS58255B1 (pt)
RU (1) RU2676708C2 (pt)
SG (2) SG11201508028QA (pt)
SI (2) SI3456831T1 (pt)
SM (2) SMT201800671T1 (pt)
WO (1) WO2014172489A2 (pt)

Families Citing this family (166)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2612459T3 (es) 2010-08-02 2017-05-17 Regeneron Pharmaceuticals, Inc. Ratones que producen proteínas de unión que comprenden dominios VL
WO2013066438A2 (en) 2011-07-22 2013-05-10 President And Fellows Of Harvard College Evaluation and improvement of nuclease cleavage specificity
DK2847335T3 (en) * 2012-04-25 2018-08-13 Regeneron Pharma NUCLEASED MEDIUM TARGETING WITH LARGE TARGET VECTORS
LT2800811T (lt) 2012-05-25 2017-09-11 The Regents Of The University Of California Būdai ir kompozicijos, skirti tikslinės dnr modifikavimui, panaudojant adresuotą rnr, ir transkripcijos moduliavimui, panaudojant adresuotą rnr
PT3138912T (pt) 2012-12-06 2018-12-28 Sigma Aldrich Co Llc Modificação e regulação de genoma baseado em crispr
JP6475172B2 (ja) 2013-02-20 2019-02-27 リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. ラットの遺伝子組換え
WO2014152432A2 (en) 2013-03-15 2014-09-25 The General Hospital Corporation Rna-guided targeting of genetic and epigenomic regulatory proteins to specific genomic loci
US10760064B2 (en) 2013-03-15 2020-09-01 The General Hospital Corporation RNA-guided targeting of genetic and epigenomic regulatory proteins to specific genomic loci
LT2986729T (lt) 2013-04-16 2018-10-25 Regeneron Pharmaceuticals, Inc. Žiurkės genomo tikslinė modifikacija
US10011850B2 (en) 2013-06-21 2018-07-03 The General Hospital Corporation Using RNA-guided FokI Nucleases (RFNs) to increase specificity for RNA-Guided Genome Editing
CN105392885B (zh) * 2013-07-19 2020-11-03 赖瑞克斯生物科技公司 用于产生双等位基因敲除的方法和组合物
EP3030653A4 (en) 2013-08-07 2017-07-26 Regeneron Pharmaceuticals, Inc. Lincrna-deficient non-human animals
US9163284B2 (en) 2013-08-09 2015-10-20 President And Fellows Of Harvard College Methods for identifying a target site of a Cas9 nuclease
US9359599B2 (en) 2013-08-22 2016-06-07 President And Fellows Of Harvard College Engineered transcription activator-like effector (TALE) domains and uses thereof
US9526784B2 (en) 2013-09-06 2016-12-27 President And Fellows Of Harvard College Delivery system for functional nucleases
US9388430B2 (en) 2013-09-06 2016-07-12 President And Fellows Of Harvard College Cas9-recombinase fusion proteins and uses thereof
US9228207B2 (en) 2013-09-06 2016-01-05 President And Fellows Of Harvard College Switchable gRNAs comprising aptamers
TW201542816A (zh) * 2013-09-18 2015-11-16 Kymab Ltd 方法、細胞與生物體
DK3066201T3 (en) 2013-11-07 2018-06-06 Editas Medicine Inc CRISPR-RELATED PROCEDURES AND COMPOSITIONS WITH LEADING GRADES
CN105980568B (zh) 2013-12-11 2019-12-03 瑞泽恩制药公司 用于靶向修饰基因组的方法和组合物
HUE041331T2 (hu) * 2013-12-11 2019-05-28 Regeneron Pharma Módszerek és készítmények a genom célzott módosításához
US20150166985A1 (en) 2013-12-12 2015-06-18 President And Fellows Of Harvard College Methods for correcting von willebrand factor point mutations
BR112016021679A2 (pt) 2014-03-21 2018-12-04 Regeneron Pharmaceuticals, Inc. proteína de ligação ao antígeno, métodos de produção de uma proteína de ligação ao antígeno e de identificação de uma ou mais proteínas de ligação ao antígeno, hibridoma, ácido nucleico, célula, e, animal não humano geneticamente modificado.
MX2016012274A (es) 2014-03-21 2017-05-23 Regeneron Pharma Animales no humanos que producen proteinas de union de dominio simple.
BR112016026245A2 (pt) 2014-05-30 2018-02-20 Regeneron Pharma ?roedor, e, métodos para fazer um roedor humanizado, para fazer um camundongo com dpp4 humanizado, para fazer um roedor transgênico humanizado e para determinar a eficácia terapêutica in vivo de um antagonista da dpp4 específica para humanos no roedor?
KR102374379B1 (ko) 2014-06-06 2022-03-17 리제너론 파마슈티칼스 인코포레이티드 표적화된 좌를 변형시키는 방법 및 조성물
AU2015280069B2 (en) 2014-06-23 2021-08-12 The General Hospital Corporation Genomewide unbiased identification of dsbs evaluated by sequencing (guide-seq)
CA3172866A1 (en) 2014-06-26 2015-12-30 Regeneron Pharamaceuticals, Inc. Methods and compositions for targeted genetic modifications and methods of use
CA2956224A1 (en) 2014-07-30 2016-02-11 President And Fellows Of Harvard College Cas9 proteins including ligand-dependent inteins
EP3561052A1 (en) 2014-10-15 2019-10-30 Regeneron Pharmaceuticals, Inc. Methods and compositions for generating or maintaining pluripotent cells
ES2731437T3 (es) * 2014-11-21 2019-11-15 Regeneron Pharma Métodos y composiciones para la modificación genética dirigida mediante el uso de pares de ARN guías
CA2969619A1 (en) 2014-12-03 2016-06-09 Agilent Technologies, Inc. Guide rna with chemical modifications
LT3230320T (lt) * 2014-12-09 2021-01-11 Regeneron Pharmaceuticals, Inc. Gyvūnai, išskyrus žmogų, turintys humanizuotą diferenciacijos klasterio 274 geną
US11326184B2 (en) * 2014-12-19 2022-05-10 Regeneron Pharmaceuticals, Inc. Methods and compositions for targeted genetic modification through single-step multiple targeting
US11208638B2 (en) 2015-01-12 2021-12-28 The Regents Of The University Of California Heterodimeric Cas9 and methods of use thereof
US11180792B2 (en) 2015-01-28 2021-11-23 The Regents Of The University Of California Methods and compositions for labeling a single-stranded target nucleic acid
US10202589B2 (en) 2015-03-03 2019-02-12 The General Hospital Corporation Engineered CRISPR-Cas9 nucleases with altered PAM specificity
KR102424119B1 (ko) 2015-03-16 2022-07-25 리제너론 파마슈티칼스 인코포레이티드 저하된 상위 및 하위 운동 뉴런 기능 및 감각 지각을 나타내는 비-인간 동물
WO2016149678A1 (en) 2015-03-19 2016-09-22 Regeneron Pharmaceuticals, Inc. Non-human animals that select for light chain variable regions that bind antigen
KR102648489B1 (ko) 2015-04-06 2024-03-15 더 보드 어브 트러스티스 어브 더 리랜드 스탠포드 주니어 유니버시티 Crispr/cas-매개 유전자 조절을 위한 화학적으로 변형된 가이드 rna
ES2784360T3 (es) 2015-05-29 2020-09-24 Regeneron Pharma Animales no humanos que tienen una interrupción en un locus C9ORF72
WO2016196655A1 (en) 2015-06-03 2016-12-08 The Regents Of The University Of California Cas9 variants and methods of use thereof
US9512446B1 (en) 2015-08-28 2016-12-06 The General Hospital Corporation Engineered CRISPR-Cas9 nucleases
WO2017040348A1 (en) 2015-08-28 2017-03-09 The General Hospital Corporation Engineered crispr-cas9 nucleases
US9926546B2 (en) 2015-08-28 2018-03-27 The General Hospital Corporation Engineered CRISPR-Cas9 nucleases
US10412939B2 (en) 2015-09-02 2019-09-17 Regeneron Pharmaceuticals, Inc. Rodent model of prostate cancer
CA3000816A1 (en) 2015-09-11 2017-03-16 The General Hospital Corporation Full interrogation of nuclease dsbs and sequencing (find-seq)
CN105177110A (zh) * 2015-09-11 2015-12-23 中国科学院微生物研究所 核酸的检测方法
WO2017053729A1 (en) 2015-09-25 2017-03-30 The Board Of Trustees Of The Leland Stanford Junior University Nuclease-mediated genome editing of primary cells and enrichment thereof
US9850484B2 (en) 2015-09-30 2017-12-26 The General Hospital Corporation Comprehensive in vitro reporting of cleavage events by sequencing (Circle-seq)
JP7067793B2 (ja) 2015-10-23 2022-05-16 プレジデント アンド フェローズ オブ ハーバード カレッジ 核酸塩基編集因子およびその使用
RS61866B1 (sr) 2015-11-20 2021-06-30 Regeneron Pharma Ne-humane životinje koje imaju humanizovani gen za aktivaciju limfocita 3
WO2017143071A1 (en) 2016-02-18 2017-08-24 The Regents Of The University Of California Methods and compositions for gene editing in stem cells
EP3895529A1 (en) 2016-02-29 2021-10-20 Regeneron Pharmaceuticals, Inc. Rodents having a humanized tmprss gene
CN109414414A (zh) 2016-03-16 2019-03-01 戴维·格拉德斯通研究所 用于治疗肥胖症和/或糖尿病以及用于鉴定候选治疗剂的方法和组合物
JP7324583B2 (ja) * 2016-05-20 2023-08-10 リジェネロン・ファーマシューティカルズ・インコーポレイテッド 複数のガイドrnaを使用して免疫寛容を破綻させるための方法
US20210010022A1 (en) * 2016-05-27 2021-01-14 Cambridge Enterprise Limited Novel nucleic acid construct
JP7053499B2 (ja) 2016-06-03 2022-04-12 リジェネロン・ファーマシューティカルズ・インコーポレイテッド 外因性ターミナルデオキシヌクレオチジルトランスフェラーゼを発現する非ヒト動物
US10767175B2 (en) 2016-06-08 2020-09-08 Agilent Technologies, Inc. High specificity genome editing using chemically modified guide RNAs
US10221395B2 (en) * 2016-06-16 2019-03-05 Cedars-Sinai Medical Center Efficient method for reprogramming blood to induced pluripotent stem cells
US11572545B2 (en) 2016-06-16 2023-02-07 Cedars-Sinai Medical Center Efficient method for reprogramming blood to induced pluripotent stem cells
CA3031206A1 (en) 2016-07-29 2018-02-01 Regeneron Pharmaceuticals, Inc. Fibrillin-1 mutations for modeling neonatal progeroid syndrome with congenital lipodystrophy
GB2568182A (en) 2016-08-03 2019-05-08 Harvard College Adenosine nucleobase editors and uses thereof
EP3497214B1 (en) 2016-08-09 2023-06-28 President and Fellows of Harvard College Programmable cas9-recombinase fusion proteins and uses thereof
WO2018039438A1 (en) 2016-08-24 2018-03-01 President And Fellows Of Harvard College Incorporation of unnatural amino acids into proteins using base editing
CN107815465B (zh) 2016-08-31 2021-03-16 百奥赛图(北京)医药科技股份有限公司 人源化基因改造动物模型的制备方法及应用
WO2018041119A1 (en) * 2016-08-31 2018-03-08 Beijing Biocytogen Co., Ltd Genetically modified non-human animal with human or chimeric ox40
EA201990861A1 (ru) 2016-09-30 2019-09-30 Те Риджентс Оф Те Юниверсити Оф Калифорния Рнк-направляемые модифицирующие нуклеиновые кислоты ферменты и способы их применения
RU2760877C2 (ru) 2016-09-30 2021-12-01 Регенерон Фармасьютикалс, Инк. Животные, отличные от человека, характеризующиеся экспансией гексануклеотидных повторов в локусе c9orf72
US10669539B2 (en) 2016-10-06 2020-06-02 Pioneer Biolabs, Llc Methods and compositions for generating CRISPR guide RNA libraries
GB2573062A (en) 2016-10-14 2019-10-23 Harvard College AAV delivery of nucleobase editors
KR20240172763A (ko) 2016-12-14 2024-12-10 리간달 인코포레이티드 핵산 및/또는 단백질 적재물 전달을 위한 조성물 및 방법
US10745677B2 (en) 2016-12-23 2020-08-18 President And Fellows Of Harvard College Editing of CCR5 receptor gene to protect against HIV infection
CN118140872A (zh) 2017-01-19 2024-06-07 欧莫诺艾比公司 来自具有多个重链免疫球蛋白基因座的转基因啮齿类动物的人抗体
JP7203427B2 (ja) 2017-02-14 2023-01-13 ユニバーシティ オブ ピッツバーグ - オブ ザ コモンウェルス システム オブ ハイヤー エデュケイション ヒト人工多能性幹細胞を操作して肝臓組織を作製する方法
WO2018157058A1 (en) 2017-02-27 2018-08-30 Regeneron Pharmaceuticals, Inc. Non-human animal models of retinoschisis
EP3592853A1 (en) 2017-03-09 2020-01-15 President and Fellows of Harvard College Suppression of pain by gene editing
US11542496B2 (en) 2017-03-10 2023-01-03 President And Fellows Of Harvard College Cytosine to guanine base editor
CN108467873B (zh) * 2017-03-17 2020-03-13 百奥赛图江苏基因生物技术有限公司 一种cd132基因缺失的免疫缺陷动物模型的制备方法及应用
US11268082B2 (en) 2017-03-23 2022-03-08 President And Fellows Of Harvard College Nucleobase editors comprising nucleic acid programmable DNA binding proteins
CN106987604B (zh) * 2017-03-29 2021-05-28 北京希诺谷生物科技有限公司 一种制备动脉粥样硬化疾病模型犬的方法
US12060572B2 (en) 2017-04-20 2024-08-13 Ramot At Tel-Aviv University Ltd. Recombination activating gene (RAG) induced V(D)J gene targeting
US11591589B2 (en) 2017-04-21 2023-02-28 The General Hospital Corporation Variants of Cpf1 (Cas12a) with altered PAM specificity
WO2018209320A1 (en) 2017-05-12 2018-11-15 President And Fellows Of Harvard College Aptazyme-embedded guide rnas for use with crispr-cas9 in genome editing and transcriptional activation
AU2018272067B2 (en) 2017-05-25 2024-07-18 The General Hospital Corporation Base editors with improved precision and specificity
CN109136273B (zh) * 2017-06-16 2022-09-27 中国科学院分子细胞科学卓越创新中心 制备免疫缺陷的大鼠的方法及其应用
CN111801345A (zh) 2017-07-28 2020-10-20 哈佛大学的校长及成员们 使用噬菌体辅助连续进化(pace)的进化碱基编辑器的方法和组合物
EP3585160A2 (en) 2017-07-31 2020-01-01 Regeneron Pharmaceuticals, Inc. Crispr reporter non-human animals and uses thereof
JP7359753B2 (ja) 2017-07-31 2023-10-11 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Casトランスジェニックマウスの胚性幹細胞およびマウスならびにその使用
BR112020003596A2 (pt) 2017-08-23 2020-09-01 The General Hospital Corporation nucleases de crispr-cas9 engenheiradas com especificidade de pam alterada
WO2019139645A2 (en) 2017-08-30 2019-07-18 President And Fellows Of Harvard College High efficiency base editors comprising gam
CN111315889A (zh) * 2017-09-08 2020-06-19 生命技术公司 提高同源重组的方法和其组合物
BR112020006428A2 (pt) * 2017-09-28 2020-09-24 Toolgen Incorporated manipulação de genoma artificial para regulação de expressão de genes
US11572574B2 (en) 2017-09-28 2023-02-07 Toolgen Incorporated Artificial genome manipulation for gene expression regulation
NZ762942A (en) 2017-09-29 2024-10-25 Intellia Therapeutics Inc Compositions and methods for ttr gene editing and treating attr amyloidosis
RU2020112751A (ru) 2017-09-29 2021-10-29 Регенерон Фармасьютикалз, Инк. Отличные от человека животные, у которых экспрессируется гуманизированный комплекс c1q
CN111163633B (zh) 2017-09-29 2022-09-09 瑞泽恩制药公司 包含人源化ttr基因座的非人类动物及其使用方法
US11725228B2 (en) 2017-10-11 2023-08-15 The General Hospital Corporation Methods for detecting site-specific and spurious genomic deamination induced by base editing technologies
EP3697906A1 (en) 2017-10-16 2020-08-26 The Broad Institute, Inc. Uses of adenosine base editors
WO2019108983A1 (en) 2017-11-30 2019-06-06 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized trkb locus
MX2020005830A (es) 2017-12-05 2020-08-20 Regeneron Pharma Animales no humanos que tienen una cadena ligera lambda de inmunoglobulina modificada y usos de estos.
WO2020172587A1 (en) * 2019-02-21 2020-08-27 Nemametrix Inc Monogenic or polygenic disease model organisms humanized with two or more genes
EP3592140A1 (en) 2018-03-19 2020-01-15 Regeneron Pharmaceuticals, Inc. Transcription modulation in animals using crispr/cas systems
LT3772927T (lt) 2018-03-24 2025-02-10 Regeneron Pharmaceuticals, Inc. Genetiškai modifikuotos pelės arba žiurkės, skirtos gaminti terapinius antikūnus prieš peptidų- mhc kompleksus, jų gamybos būdai ir panaudojimas
CN112105260B (zh) 2018-03-26 2023-04-28 瑞泽恩制药公司 用于测试治疗剂的人源化啮齿动物
CN112204148B (zh) * 2018-03-27 2024-04-30 宾夕法尼亚大学董事会 具有增强功能的修饰的免疫细胞及其筛选方法
WO2019204378A1 (en) 2018-04-17 2019-10-24 The General Hospital Corporation Sensitive in vitro assays for substrate preferences and sites of nucleic acid binding, modifying, and cleaving agents
CN108624622A (zh) * 2018-05-16 2018-10-09 湖南艾佳生物科技股份有限公司 一种基于CRISPR-Cas9系统构建的能分泌小鼠白细胞介素-6的基因工程细胞株
EP3797160A1 (en) 2018-05-23 2021-03-31 The Broad Institute Inc. Base editors and uses thereof
CN109868285A (zh) * 2018-05-29 2019-06-11 江苏艾尔康生物医药科技有限公司 一种免疫缺陷大鼠动物模型的构建方法及应用
US10463029B1 (en) 2018-06-07 2019-11-05 Regeneron Pharmaceuticals, Inc. Rodent model of steel syndrome
MX2020013545A (es) 2018-06-13 2021-02-26 Regeneron Pharma Modelo en roedores de fibrodisplasia osificante progresiva.
IL318469A (en) 2018-06-14 2025-03-01 Regeneron Pharma Non-human animals capable of reorganizing transgenic DH-DH, and their uses
CA3105658A1 (en) 2018-07-13 2020-01-16 The Regents Of The University Of California Retrotransposon-based delivery vehicle and methods of use thereof
AU2019308205A1 (en) 2018-07-16 2020-11-19 Regeneron Pharmaceuticals, Inc. Non-human animal models of DITRA disease and uses thereof
CN113286880A (zh) * 2018-08-28 2021-08-20 旗舰先锋创新Vi有限责任公司 调控基因组的方法和组合物
US20220053741A1 (en) 2018-09-13 2022-02-24 Regeneron Pharmaceuticals, Inc. Complement Factor H Gene Knockout Rat as a Model of C3 Glomerulopathy
US11407995B1 (en) 2018-10-26 2022-08-09 Inari Agriculture Technology, Inc. RNA-guided nucleases and DNA binding proteins
US11434477B1 (en) 2018-11-02 2022-09-06 Inari Agriculture Technology, Inc. RNA-guided nucleases and DNA binding proteins
CN109504708A (zh) * 2018-12-03 2019-03-22 江苏集萃药康生物科技有限公司 一种筛选标记自我删除的基因打靶载体及方法
EP3732291A1 (en) 2018-12-20 2020-11-04 Regeneron Pharmaceuticals, Inc. Nuclease-mediated repeat expansion
KR20210116480A (ko) 2019-01-17 2021-09-27 리제너론 파마슈티칼스 인코포레이티드 기분 장애의 설치류 모델
WO2020163396A1 (en) 2019-02-04 2020-08-13 The General Hospital Corporation Adenine dna base editor variants with reduced off-target rna editing
WO2020163856A1 (en) 2019-02-10 2020-08-13 The J. David Gladstone Institutes, A Testamentary Trust Established Under The Will Of J. David Gladstone Modified mitochondrion and methods of use thereof
AU2020226445A1 (en) 2019-02-18 2021-07-08 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. Genetically modified non-human animals with humanized immunoglobulin locus
CA3127153A1 (en) 2019-02-22 2020-08-27 Regeneron Pharmaceuticals, Inc. Rodents having genetically modified sodium channels and methods of use thereof
AU2020231380A1 (en) 2019-03-07 2021-09-23 The Regents Of The University Of California CRISPR-Cas effector polypeptides and methods of use thereof
EP3937626A1 (en) 2019-03-15 2022-01-19 Regeneron Pharmaceuticals, Inc. A loss of function rodent model of solute carrier 39 member 5
WO2020191248A1 (en) 2019-03-19 2020-09-24 The Broad Institute, Inc. Method and compositions for editing nucleotide sequences
AU2020253532B2 (en) 2019-04-04 2024-06-20 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized coagulation factor 12 locus
CN113874510A (zh) 2019-06-04 2021-12-31 瑞泽恩制药公司 包括具有β滑移突变的人源化TTR基因座的非人动物和使用方法
AU2020289554A1 (en) 2019-06-05 2021-11-18 Regeneron Pharmaceuticals, Inc. Non-human animals having a limited lambda light chain repertoire expressed from the kappa locus and uses thereof
BR112021022722A2 (pt) 2019-06-07 2022-01-04 Regeneron Pharma Animal não humano, célula de animal não humana, genoma de animal não humano, gene de albumina animal não humana humanizada, vetor de alvejamento, método de avaliação da atividade de um reagente, e, método de otimização da atividade de um reagente
CN114008193A (zh) 2019-06-27 2022-02-01 瑞泽恩制药公司 Tdp-43蛋白病的建模
AU2020358847A1 (en) 2019-10-03 2022-04-21 Regeneron Pharmaceuticals, Inc. A Crnn loss of function rodent model
WO2021108363A1 (en) 2019-11-25 2021-06-03 Regeneron Pharmaceuticals, Inc. Crispr/cas-mediated upregulation of humanized ttr allele
CN114786479B (zh) * 2019-12-25 2023-12-15 江苏集萃药康生物科技股份有限公司 一种il-15人源化小鼠模型及其用途
JP2023511626A (ja) 2020-01-28 2023-03-20 リジェネロン・ファーマシューティカルズ・インコーポレイテッド ヒト化pnpla3遺伝子座を含む非ヒト動物および使用方法
EP4099821A1 (en) 2020-02-07 2022-12-14 Regeneron Pharmaceuticals, Inc. <smallcaps/>? ? ?klkb1? ? ? ? ?non-human animals comprising a humanizedlocus and methods of use
EP4114173A1 (en) 2020-03-04 2023-01-11 Regeneron Pharmaceuticals, Inc. A rodent model of b4galt1-mediated functions
CN113355323B (zh) * 2020-03-06 2023-07-11 生物岛实验室 人源化ace2基因改造小鼠模型的制备方法及应用
CN113355325B (zh) * 2020-03-06 2023-07-14 中国科学院广州生物医药与健康研究院 人源化ace2基因改造小鼠胚胎干细胞模型制备方法及应用
WO2021195079A1 (en) 2020-03-23 2021-09-30 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ttr locus comprising a v30m mutation and methods of use
US20230172170A1 (en) 2020-04-21 2023-06-08 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized cxcl13 gene
EP4146804A1 (en) 2020-05-08 2023-03-15 The Broad Institute Inc. Methods and compositions for simultaneous editing of both strands of a target double-stranded nucleotide sequence
IL298632A (en) 2020-06-02 2023-01-01 Biocytogen Pharmaceuticals Beijing Co Ltd Genetically modified non-human animals with common light chain immunoglobulin locus
US12082566B2 (en) 2020-10-01 2024-09-10 Regeneron Pharmaceuticals, Inc. Rodent animals expressing human CR1
KR20230124973A (ko) 2020-12-21 2023-08-28 리제너론 파마슈티칼스 인코포레이티드 인간화 tslp 유전자, 인간화 tslp 수용체 유전자, 및/또는인간화 il7ra 유전자를 갖는 비인간 동물
CN112852875B (zh) * 2021-02-26 2022-10-21 福建省立医院 示踪肿瘤T淋巴细胞浸润的CD3e转基因小鼠模型的构建方法
CN113229213B (zh) * 2021-05-14 2022-06-14 福州大学 通过近红外荧光探针标记血栓实现肺栓塞造模及无创定量检测的方法
WO2023039586A1 (en) 2021-09-10 2023-03-16 Agilent Technologies, Inc. Guide rnas with chemical modification for prime editing
EP4426832A1 (en) 2021-11-03 2024-09-11 The J. David Gladstone Institutes, A Testamentary Trust Established under The Will of J. David Gladstone Precise genome editing using retrons
IL312971A (en) 2021-12-08 2024-07-01 Regeneron Pharma Mutant myocilin disease model and uses thereof
US20230279442A1 (en) 2021-12-15 2023-09-07 Versitech Limited Engineered cas9-nucleases and method of use thereof
WO2023141602A2 (en) 2022-01-21 2023-07-27 Renagade Therapeutics Management Inc. Engineered retrons and methods of use
WO2023150798A1 (en) 2022-02-07 2023-08-10 Regeneron Pharmaceuticals, Inc. Compositions and methods for defining optimal treatment timeframes in lysosomal disease
US20230257432A1 (en) 2022-02-11 2023-08-17 Regeneron Pharmaceuticals, Inc. Compositions and methods for screening 4r tau targeting agents
EP4514125A1 (en) 2022-04-26 2025-03-05 Regeneron Pharmaceuticals, Inc. A rodent model of fibrodysplasia ossificans progressiva
WO2023235677A1 (en) 2022-05-31 2023-12-07 Regeneron Pharmaceuticals, Inc. Animal model of tdp-43 proteinopathy
US20230417899A1 (en) 2022-06-27 2023-12-28 Oshkosh Corporation Position tracking for a lift device
AU2023311964A1 (en) 2022-07-18 2025-01-30 Renagade Therapeutics Management Inc. Gene editing components, systems, and methods of use
US20240102045A1 (en) 2022-07-19 2024-03-28 Regeneron Pharmaceuticals, Inc. Vectors, genetically modified cells, and genetically modified non-human animals comprising the same
WO2024044723A1 (en) 2022-08-25 2024-02-29 Renagade Therapeutics Management Inc. Engineered retrons and methods of use
WO2024073679A1 (en) 2022-09-29 2024-04-04 Regeneron Pharmaceuticals, Inc. Correction of hepatosteatosis in humanized liver animals through restoration of il6/il6r/gp130 signaling in human hepatocytes
US20240415103A1 (en) 2023-06-16 2024-12-19 Regeneron Pharmaceuticals, Inc. Vectors, genetically modified cells, and genetically modified non-human animals comprising the same
WO2025049959A2 (en) 2023-09-01 2025-03-06 Renagade Therapeutics Management Inc. Gene editing systems, compositions, and methods for treatment of vexas syndrome

Family Cites Families (229)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT87133B (pt) 1987-04-02 1992-07-31 Amrad Corp Ltd Metodo de purificacao do factor inibidor da leucemia (lif) e de composicoes farmaceuticas contendo polipeptidos com actividade do lif
WO1995006716A1 (en) 1993-08-30 1995-03-09 Northwestern University Rat pluripotent embryonic stem cells and method of obtaining and using same
CA2246712A1 (en) 1996-02-16 1997-08-21 The University Of Edinburgh Cytokine expressed by dia/lif-deficient embryonic stem cells for the inhibition of differentiation
US5830729A (en) 1996-04-18 1998-11-03 Institut Pasteur I Sce I-induced gene replacement and gene conversion in embryonic stem cells
US6136566A (en) 1996-10-04 2000-10-24 Lexicon Graphics Incorporated Indexed library of cells containing genomic modifications and methods of making and utilizing the same
AU8587598A (en) 1997-07-26 1999-02-16 Wisconsin Alumni Research Foundation Trans-species nuclear transfer
WO2000039316A1 (en) * 1998-12-31 2000-07-06 The J. David Gladstone Institutes Transgenic rodents and rodent cell lines expressing hiv co-receptors
US6599692B1 (en) 1999-09-14 2003-07-29 Sangamo Bioscience, Inc. Functional genomics using zinc finger proteins
US6503717B2 (en) 1999-12-06 2003-01-07 Sangamo Biosciences, Inc. Methods of using randomized libraries of zinc finger proteins for the identification of gene function
EP1147209A2 (en) 1999-02-03 2001-10-24 The Children's Medical Center Corporation Gene repair involving the induction of double-stranded dna cleavage at a chromosomal target site
US20030104526A1 (en) 1999-03-24 2003-06-05 Qiang Liu Position dependent recognition of GNN nucleotide triplets by zinc fingers
US20050144655A1 (en) 2000-10-31 2005-06-30 Economides Aris N. Methods of modifying eukaryotic cells
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US6586251B2 (en) * 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US7105348B2 (en) 2000-10-31 2006-09-12 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
AU2884102A (en) 2000-12-07 2002-06-18 Sangamo Biosciences Inc Regulation of angiogenesis with zinc finger proteins
US20030093818A1 (en) 2000-12-19 2003-05-15 Belmont Heather J. Transgenic animals comprising a humanized immune system
WO2002057294A2 (en) 2001-01-22 2002-07-25 Sangamo Biosciences, Inc. Zinc finger proteins for dna binding and gene regulation in plants
AU2002225187A1 (en) 2001-01-22 2002-07-30 Sangamo Biosciences, Inc. Zinc finger polypeptides and their use
DK1491093T3 (da) 2001-02-14 2013-10-28 Abt Holding Co Multipotente voksne stamceller, kilder dertil, fremgangsmåder til fremskaffelse og vedligeholdelse af samme, fremgangsmåder til differentiering deraf, fremgangsmåder til anvendelse deraf samt celler afledt deraf
AUPR451401A0 (en) 2001-04-20 2001-05-24 Monash University A method of nuclear transfer
CA2474486C (en) 2002-01-23 2013-05-14 The University Of Utah Research Foundation Targeted chromosomal mutagenesis using zinc finger nucleases
DE60316124T3 (de) 2002-03-15 2018-03-22 Cellectis Hybride and einzelkettige meganukleasen und deren anwendungen
EP2368982A3 (en) 2002-03-21 2011-10-12 Sangamo BioSciences, Inc. Methods and compositions for using zinc finger endonucleases to enhance homologous recombination
US7612250B2 (en) 2002-07-29 2009-11-03 Trustees Of Tufts College Nuclear transfer embryo formation method
JP2006502748A (ja) 2002-09-05 2006-01-26 カリフォルニア インスティテュート オブ テクノロジー 遺伝子ターゲッティングを誘発するキメラヌクレアーゼの使用方法
WO2004031346A2 (en) 2002-09-06 2004-04-15 Fred Hutchinson Cancer Research Center Methods and compositions concerning designed highly-specific nucleic acid binding proteins
US20030175968A1 (en) 2002-10-30 2003-09-18 Golic Kent G. Gene targeting method
US7344886B2 (en) 2002-11-29 2008-03-18 Boehringer Ingelheim Pharma Gmbh & Co., Kg Neomycin-phosphotransferase-genes and methods for the selection of recombinant cells producing high levels of a desired gene product
WO2004063356A2 (en) 2003-01-13 2004-07-29 Rao Mahendra S Persistent expression of candidate molecule in proliferating stem and progenitor cells for delivery of therapeutic products
GB2398784B (en) 2003-02-26 2005-07-27 Babraham Inst Removal and modification of the immunoglobulin constant region gene cluster of a non-human mammal
WO2005001087A2 (en) 2003-06-11 2005-01-06 Regeneron Pharmaceuticals, Inc. Methods of modifying genes in eukaryotic cells
US8409861B2 (en) 2003-08-08 2013-04-02 Sangamo Biosciences, Inc. Targeted deletion of cellular DNA sequences
US7888121B2 (en) 2003-08-08 2011-02-15 Sangamo Biosciences, Inc. Methods and compositions for targeted cleavage and recombination
EP1726640B1 (en) 2004-03-04 2016-01-13 Sumitomo Dainippon Pharma Co., Ltd. Rat embryonic stem cell
EP1591521A1 (en) 2004-04-30 2005-11-02 Cellectis I-Dmo I derivatives with enhanced activity at 37 degrees C and use thereof
WO2006028723A1 (en) 2004-09-03 2006-03-16 Moraga Biotechnology Inc. Non-embryonic totipotent blastomer-like stem cells and methods therefor
KR20070060115A (ko) 2004-09-16 2007-06-12 상가모 바이오사이언스 인코포레이티드 단백질 생산을 위한 조성물 및 방법
PT2767161T (pt) 2004-10-19 2018-04-20 Regeneron Pharma Método para gerar um animal homozigótico para uma modificação genética
FR2879622B1 (fr) 2004-12-17 2008-02-01 Agronomique Inst Nat Rech Procede in vitro de production d'ovocytes ou d'oeufs presentant une modification genomique ciblee
WO2006097784A1 (en) 2005-03-15 2006-09-21 Cellectis I-crei meganuclease variants with modified specificity, method of preparation and uses thereof
EP1863909B2 (en) 2005-03-15 2014-09-10 Cellectis I-crei meganuclease variants with modified specificity, method of preparation and uses thereof
US10022457B2 (en) 2005-08-05 2018-07-17 Gholam A. Peyman Methods to regulate polarization and enhance function of cells
JP5680850B2 (ja) 2006-03-30 2015-03-04 ザ・ユニバーシティ・コート・オブ・ザ・ユニバーシティ・オブ・エディンバラThe University Court of the University of Edinburgh キナーゼインヒビターを含む培養培地およびその使用
GB0615327D0 (en) 2006-03-30 2006-09-13 Univ Edinburgh Culture medium containing kinase inhibitors and uses thereof
JP5514539B2 (ja) * 2006-03-31 2014-06-04 メダレックス・リミテッド・ライアビリティ・カンパニー ヒト抗体の調製に用いるためのキメラ抗体を発現するトランスジェニック動物
CN101117633B (zh) 2006-08-03 2011-07-20 上海交通大学附属儿童医院 一种细胞核移植方法
EP2415872B1 (en) 2006-12-14 2016-05-11 Dow AgroSciences LLC Optimized non-canonical zinc finger proteins
US7771967B2 (en) * 2006-12-22 2010-08-10 The J. David Gladstone Institutes Nucleic acid encoding apolipoprotein E-I3
US10155038B2 (en) 2007-02-02 2018-12-18 Yale University Cells prepared by transient transfection and methods of use thereof
ATE489465T1 (de) 2007-04-26 2010-12-15 Sangamo Biosciences Inc Gezielte integration in die ppp1r12c-position
SG10201509853UA (en) 2007-06-01 2015-12-30 Omt Inc Compositions and methods for inhibiting endogenous immunoglobulin genes and producing transgenic human idiotype antibodies
EP2789691B1 (en) 2008-08-22 2018-08-08 Sangamo Therapeutics, Inc. Methods and compositions for targeted single-stranded cleavage and targeted integration
US20100076057A1 (en) 2008-09-23 2010-03-25 Northwestern University TARGET DNA INTERFERENCE WITH crRNA
EP2180058A1 (en) 2008-10-23 2010-04-28 Cellectis Meganuclease recombination system
US20110030072A1 (en) 2008-12-04 2011-02-03 Sigma-Aldrich Co. Genome editing of immunodeficiency genes in animals
EP3156494B8 (en) * 2008-12-04 2018-09-19 Sangamo Therapeutics, Inc. Genome editing in rats using zinc-finger nucleases
ES2645869T3 (es) 2008-12-17 2017-12-11 The Scripps Research Institute Generación y mantenimiento de células madre
US20110239315A1 (en) 2009-01-12 2011-09-29 Ulla Bonas Modular dna-binding domains and methods of use
EP2206723A1 (en) 2009-01-12 2010-07-14 Bonas, Ulla Modular DNA-binding domains
US8871905B2 (en) 2009-03-20 2014-10-28 Sangamo Biosciences, Inc. Modification of CXCR4 using engineered zinc finger proteins
US8722964B2 (en) 2009-04-23 2014-05-13 Transposagen Biopharmaceuticals, Inc. Genetically engineered or transgenic rats exhibiting a cancer phenotype due to a disruption of germline tumor suppressor genes
US8772008B2 (en) 2009-05-18 2014-07-08 Sangamo Biosciences, Inc. Methods and compositions for increasing nuclease activity
WO2011002988A1 (en) 2009-07-01 2011-01-06 Transposagen Biopharmaceuticals, Inc. Genetically modified rat models for severe combined immunodeficiency (scid)
CN102858985A (zh) * 2009-07-24 2013-01-02 西格马-奥尔德里奇有限责任公司 基因组编辑方法
CA2767377A1 (en) 2009-07-24 2011-01-27 Sigma-Aldrich Co. Llc Method for genome editing
US8558055B2 (en) 2009-07-24 2013-10-15 Transposagen Biopharmaceuticals, Inc. Genetically modified rat comprising a cytokine gene disruption and exhibiting a greater susceptibility to a cytokine-mediated autoimmune and/or inflammatory disease
WO2011017293A2 (en) 2009-08-03 2011-02-10 The General Hospital Corporation Engineering of zinc finger arrays by context-dependent assembly
US8354389B2 (en) 2009-08-14 2013-01-15 Regeneron Pharmaceuticals, Inc. miRNA-regulated differentiation-dependent self-deleting cassette
CA2779337A1 (en) 2009-10-28 2011-05-05 Helmholtz Zentrum Muenchen Deutsches Forschungszentrum Fuer Gesundheit U Nd Umwelt (Gmbh) Homologous recombination in the oocyte
ES2613662T3 (es) 2009-10-29 2017-05-25 Regeneron Pharmaceuticals, Inc. Alelos multifuncionales
WO2011053957A2 (en) 2009-11-02 2011-05-05 Gen9, Inc. Compositions and methods for the regulation of multiple genes of interest in a cell
EP2508595B1 (en) 2009-12-01 2016-11-23 National Cancer Center Method for constructing chimeric rat using rat embryonic stem cells
WO2011072246A2 (en) 2009-12-10 2011-06-16 Regents Of The University Of Minnesota Tal effector-mediated dna modification
ES2583060T3 (es) 2009-12-21 2016-09-16 Keygene N.V. Técnicas mejoradas para la transfección de protoplastos
PH12012501467B1 (en) 2010-01-22 2018-07-04 Corteva Agriscience Llc Excision of transgenes in genetically modified organisms
EP2660318A1 (en) 2010-02-09 2013-11-06 Sangamo BioSciences, Inc. Targeted genomic modification with partially single-stranded donor molecules
CN103025344B (zh) 2010-05-17 2016-06-29 桑格摩生物科学股份有限公司 新型dna-结合蛋白及其用途
GB201009732D0 (en) 2010-06-10 2010-07-21 Gene Bridges Gmbh Direct cloning
SG185703A1 (en) 2010-06-11 2013-01-30 Regeneron Pharma Production of fertile xy female animals from xy es cells
AU2011281062B2 (en) 2010-07-21 2015-01-22 Board Of Regents, The University Of Texas System Methods and compositions for modification of a HLA locus
WO2012018726A1 (en) 2010-08-02 2012-02-09 Cellectis Sa Method for increasing double-strand break-induced gene targeting
EP2618656B1 (en) 2010-09-20 2018-06-20 Yale University, Inc. HUMAN SIRPalpha TRANSGENIC ANIMALS AND THEIR METHODS OF USE
MX338971B (es) 2011-02-15 2016-05-06 Inst Res Biomedicine Irb Ratones de m-csf humanizada.
WO2012129198A1 (en) * 2011-03-23 2012-09-27 Transposagen Biopharmaceuticals, Inc. Genetically modified rat models for obesity and diabetes
WO2012168307A2 (en) 2011-06-07 2012-12-13 Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Improved recombination efficiency by inhibition of nhej dna repair
WO2013032918A1 (en) * 2011-08-26 2013-03-07 Yecuris Corporation Fumarylacetoacetate hydrolase (fah)-deficient and immunodeficient rats and uses thereof
MX379517B (es) 2011-10-28 2025-03-10 Regeneron Pharmaceuticals Inc Ratones con receptor de linfocitos t modificados genéticamente.
WO2013141680A1 (en) 2012-03-20 2013-09-26 Vilnius University RNA-DIRECTED DNA CLEAVAGE BY THE Cas9-crRNA COMPLEX
US9637739B2 (en) 2012-03-20 2017-05-02 Vilnius University RNA-directed DNA cleavage by the Cas9-crRNA complex
DK2847335T3 (en) 2012-04-25 2018-08-13 Regeneron Pharma NUCLEASED MEDIUM TARGETING WITH LARGE TARGET VECTORS
DE102012103797A1 (de) 2012-04-30 2013-10-31 KRAH Elektronische Bauelemente GmbH Flüssigkeitsgekühlter Widerstand
CA2871524C (en) 2012-05-07 2021-07-27 Sangamo Biosciences, Inc. Methods and compositions for nuclease-mediated targeted integration of transgenes
LT2800811T (lt) 2012-05-25 2017-09-11 The Regents Of The University Of California Būdai ir kompozicijos, skirti tikslinės dnr modifikavimui, panaudojant adresuotą rnr, ir transkripcijos moduliavimui, panaudojant adresuotą rnr
MX2014015204A (es) 2012-06-12 2015-08-07 Genentech Inc Metodos y composiciones para generar alelos con inactivacion condicional.
EP3808844A1 (en) 2012-07-25 2021-04-21 The Broad Institute, Inc. Inducible dna binding proteins and genome perturbation tools and applications thereof
CN110669758A (zh) 2012-10-23 2020-01-10 基因工具股份有限公司 用于切割靶dna 的组合物及其用途
PT3138912T (pt) 2012-12-06 2018-12-28 Sigma Aldrich Co Llc Modificação e regulação de genoma baseado em crispr
WO2014093479A1 (en) 2012-12-11 2014-06-19 Montana State University Crispr (clustered regularly interspaced short palindromic repeats) rna-guided control of gene regulation
ES2701749T3 (es) 2012-12-12 2019-02-25 Broad Inst Inc Métodos, modelos, sistemas y aparatos para identificar secuencias diana para enzimas Cas o sistemas CRISPR-Cas para secuencias diana y transmitir resultados de los mismos
WO2014093694A1 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Crispr-cas nickase systems, methods and compositions for sequence manipulation in eukaryotes
ES2786193T3 (es) 2012-12-12 2020-10-09 Broad Inst Inc Modificación por tecnología genética y optimización de sistemas, métodos y composiciones enzimáticas mejorados para la manipulación de secuencias
SG11201504523UA (en) 2012-12-12 2015-07-30 Broad Inst Inc Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications
US20140189896A1 (en) 2012-12-12 2014-07-03 Feng Zhang Crispr-cas component systems, methods and compositions for sequence manipulation
EP2931899A1 (en) 2012-12-12 2015-10-21 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof
ES2542015T3 (es) 2012-12-12 2015-07-29 The Broad Institute, Inc. Ingeniería de sistemas, métodos y composiciones de guía optimizadas para manipulación de secuencias
US20140186843A1 (en) 2012-12-12 2014-07-03 Massachusetts Institute Of Technology Methods, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof
US8697359B1 (en) 2012-12-12 2014-04-15 The Broad Institute, Inc. CRISPR-Cas systems and methods for altering expression of gene products
PT2931898E (pt) 2012-12-12 2016-06-16 Harvard College Manipulação e otimização de sistemas, métodos e composições para manipulação de sequências com domínios funcionais
CN105121641A (zh) 2012-12-17 2015-12-02 哈佛大学校长及研究员协会 Rna-引导的人类基因组工程化
EP2938184B1 (en) 2012-12-27 2018-10-31 Keygene N.V. Method for removing genetic linkage in a plant
WO2014127287A1 (en) 2013-02-14 2014-08-21 Massachusetts Institute Of Technology Method for in vivo tergated mutagenesis
JP6475172B2 (ja) 2013-02-20 2019-02-27 リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. ラットの遺伝子組換え
AU2014218621B2 (en) 2013-02-25 2019-11-07 Sangamo Therapeutics, Inc. Methods and compositions for enhancing nuclease-mediated gene disruption
EP2922393B2 (en) 2013-02-27 2022-12-28 Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Gene editing in the oocyte by cas9 nucleases
US10612043B2 (en) 2013-03-09 2020-04-07 Agilent Technologies, Inc. Methods of in vivo engineering of large sequences using multiple CRISPR/cas selections of recombineering events
EP3620534B1 (en) 2013-03-14 2021-10-13 Caribou Biosciences, Inc. Crispr-cas compositions of nucleic acid-targeting nucleic acids
US20140349400A1 (en) 2013-03-15 2014-11-27 Massachusetts Institute Of Technology Programmable Modification of DNA
US20140273230A1 (en) 2013-03-15 2014-09-18 Sigma-Aldrich Co., Llc Crispr-based genome modification and regulation
US9234213B2 (en) 2013-03-15 2016-01-12 System Biosciences, Llc Compositions and methods directed to CRISPR/Cas genomic engineering systems
WO2014153470A2 (en) 2013-03-21 2014-09-25 Sangamo Biosciences, Inc. Targeted disruption of t cell receptor genes using engineered zinc finger protein nucleases
CN115261411A (zh) 2013-04-04 2022-11-01 哈佛学院校长同事会 利用CRISPR/Cas系统的基因组编辑的治疗性用途
US20160040155A1 (en) 2013-04-16 2016-02-11 University Of Washington Through Its Center For Commercialization Activating an alternative pathway for homology-directed repair to stimulate targeted gene correction and genome engineering
US20160186208A1 (en) 2013-04-16 2016-06-30 Whitehead Institute For Biomedical Research Methods of Mutating, Modifying or Modulating Nucleic Acid in a Cell or Nonhuman Mammal
LT2986729T (lt) 2013-04-16 2018-10-25 Regeneron Pharmaceuticals, Inc. Žiurkės genomo tikslinė modifikacija
EP2796558A1 (en) 2013-04-23 2014-10-29 Rheinische Friedrich-Wilhelms-Universität Bonn Improved gene targeting and nucleic acid carrier molecule, in particular for use in plants
WO2014182700A1 (en) 2013-05-10 2014-11-13 Sangamo Biosciences, Inc. Delivery methods and compositions for nuclease-mediated genome engineering
EP2997146A4 (en) 2013-05-15 2017-04-26 Sangamo BioSciences, Inc. Methods and compositions for treatment of a genetic condition
DK3309248T3 (da) 2013-05-29 2021-08-02 Cellectis Fremgangsmåde til manipulering af T-celler til immunterapi under anvendelse af et RNA-guidet CAS-nuklease-system
AU2014273082B2 (en) 2013-05-29 2018-11-08 Cellectis A method for producing precise DNA cleavage using Cas9 nickase activity
ES2883131T3 (es) 2013-05-29 2021-12-07 Cellectis Métodos para la modificación de células T para inmunoterapia utilizando el sistema de nucleasa CAS guiado por ARN
US20140359795A1 (en) 2013-05-31 2014-12-04 Recombinetics, Inc. Genetic techniques for making animals with sortable sperm
EP3008181B1 (en) 2013-06-11 2019-11-06 The Regents of The University of California Methods and compositions for target dna modification
JP6738729B2 (ja) 2013-06-17 2020-08-12 ザ・ブロード・インスティテュート・インコーポレイテッド 分裂終了細胞の疾患および障害をターゲティングおよびモデリングするための系、方法および組成物の送達、エンジニアリングおよび最適化
ES2777217T3 (es) 2013-06-17 2020-08-04 Broad Inst Inc Suministro, modificación y optimización de sistemas de guía en tándem, métodos y composiciones para la manipulación de secuencias
KR20240172759A (ko) 2013-06-17 2024-12-10 더 브로드 인스티튜트, 인코퍼레이티드 간의 표적화 및 치료를 위한 CRISPR­Cas 시스템, 벡터 및 조성물의 전달 및 용도
EP3011035B1 (en) 2013-06-17 2020-05-13 The Broad Institute, Inc. Assay for quantitative evaluation of target site cleavage by one or more crispr-cas guide sequences
AU2014281027A1 (en) 2013-06-17 2016-01-28 Massachusetts Institute Of Technology Optimized CRISPR-Cas double nickase systems, methods and compositions for sequence manipulation
CA2915795C (en) 2013-06-17 2021-07-13 The Broad Institute, Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using viral components
US20160145645A1 (en) 2013-06-19 2016-05-26 Sigma-Aldrich Co. Llc Targeted integration
US10011850B2 (en) 2013-06-21 2018-07-03 The General Hospital Corporation Using RNA-guided FokI Nucleases (RFNs) to increase specificity for RNA-Guided Genome Editing
JP7120717B2 (ja) 2013-07-09 2022-08-17 プレジデント アンド フェローズ オブ ハーバード カレッジ 多重rna誘導型ゲノム編集
WO2015006498A2 (en) 2013-07-09 2015-01-15 President And Fellows Of Harvard College Therapeutic uses of genome editing with crispr/cas systems
SG11201600060VA (en) 2013-07-10 2016-02-26 Harvard College Orthogonal cas9 proteins for rna-guided gene regulation and editing
CN105392885B (zh) 2013-07-19 2020-11-03 赖瑞克斯生物科技公司 用于产生双等位基因敲除的方法和组合物
US11306328B2 (en) 2013-07-26 2022-04-19 President And Fellows Of Harvard College Genome engineering
BR112016003561B8 (pt) 2013-08-22 2022-11-01 Du Pont Método para a produção de uma modificação genética, método para a introdução de um polinucleotídeo de interesse no genoma de uma planta, método para a edição de um segundo gene em um genoma de planta e método para gerar uma planta de milho resistente ao glifosato
AU2014312123A1 (en) 2013-08-29 2016-03-17 Temple University Of The Commonwealth System Of Higher Education Methods and compositions for RNA-guided treatment of HIV infection
US9228207B2 (en) 2013-09-06 2016-01-05 President And Fellows Of Harvard College Switchable gRNAs comprising aptamers
US9388430B2 (en) 2013-09-06 2016-07-12 President And Fellows Of Harvard College Cas9-recombinase fusion proteins and uses thereof
TW201542816A (zh) 2013-09-18 2015-11-16 Kymab Ltd 方法、細胞與生物體
WO2015048690A1 (en) 2013-09-27 2015-04-02 The Regents Of The University Of California Optimized small guide rnas and methods of use
WO2015052231A2 (en) 2013-10-08 2015-04-16 Technical University Of Denmark Multiplex editing system
JP6646573B2 (ja) 2013-10-17 2020-02-14 サンガモ セラピューティクス, インコーポレイテッド ヌクレアーゼ媒介ゲノム遺伝子操作のための送達方法および組成物
JP5900942B2 (ja) 2013-11-06 2016-04-06 国立大学法人広島大学 核酸挿入用ベクター
DK3066201T3 (en) 2013-11-07 2018-06-06 Editas Medicine Inc CRISPR-RELATED PROCEDURES AND COMPOSITIONS WITH LEADING GRADES
US10787684B2 (en) 2013-11-19 2020-09-29 President And Fellows Of Harvard College Large gene excision and insertion
US10450586B2 (en) 2013-11-28 2019-10-22 Horizon Discovery Limited Somatic haploid human cell line
CN105980568B (zh) 2013-12-11 2019-12-03 瑞泽恩制药公司 用于靶向修饰基因组的方法和组合物
EP4219699A1 (en) 2013-12-12 2023-08-02 The Broad Institute, Inc. Engineering of systems, methods and optimized guide compositions with new architectures for sequence manipulation
SG10201804975PA (en) 2013-12-12 2018-07-30 Broad Inst Inc Delivery, Use and Therapeutic Applications of the Crispr-Cas Systems and Compositions for HBV and Viral Diseases and Disorders
EP3080260B1 (en) 2013-12-12 2019-03-06 The Broad Institute, Inc. Crispr-cas systems and methods for altering expression of gene products, structural information and inducible modular cas enzymes
MX2016007327A (es) 2013-12-12 2017-03-06 Broad Inst Inc Suministro, uso y aplicaciones terapeuticas de sistemas y composiciones crispr-cas para dirigirlos a trastornos y enfermedades usando componentes para suministro de particulas.
BR112016013520A2 (pt) 2013-12-12 2017-10-03 Broad Inst Inc Composições e métodos de uso de sistemas crispr-cas em distúrbios de repetições de nucleotídeos
EP3653229A1 (en) 2013-12-12 2020-05-20 The Broad Institute, Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for genome editing
CA2932948A1 (en) 2013-12-13 2015-06-18 Cellectis New method of selection of algal-transformed cells using nuclease
EP3083958B1 (en) 2013-12-19 2019-04-17 Amyris, Inc. Methods for genomic integration
SG10201805815YA (en) 2014-01-08 2018-08-30 Harvard College Rna-guided gene drives
EP3096609B1 (en) 2014-01-24 2021-09-22 Children's Medical Center Corporation High-throughput mouse model for optimizing antibody affinities
WO2015117041A1 (en) 2014-01-30 2015-08-06 Nair Ramesh B Gene modification-mediated methods and compositions for generating dominant traits in eukaryotic systems
US10233456B2 (en) 2014-01-30 2019-03-19 The Board Of Trustees Of The University Of Arkansas Method, vectors, cells, seeds and kits for stacking genes into a single genomic site
MX375420B (es) 2014-02-11 2025-03-06 The Regents Of The Univ Of Colorado A Body Corporate Ingenieria genetica multiplexada habilitada por crispr.
JP6606088B2 (ja) 2014-02-24 2019-11-13 サンガモ セラピューティクス, インコーポレイテッド ヌクレアーゼ媒介性標的化組み込みのための方法および組成物
EP3114227B1 (en) 2014-03-05 2021-07-21 Editas Medicine, Inc. Crispr/cas-related methods and compositions for treating usher syndrome and retinitis pigmentosa
ES2745769T3 (es) 2014-03-10 2020-03-03 Editas Medicine Inc Procedimientos y composiciones relacionados con CRISPR/CAS para tratar la amaurosis congénita de Leber 10 (LCA10)
US20170106055A1 (en) 2014-03-12 2017-04-20 Precision Biosciences, Inc. Dystrophin Gene Exon Deletion Using Engineered Nucleases
CN106455514A (zh) 2014-03-14 2017-02-22 希博斯美国有限公司 采用寡核苷酸介导的基因修复提高靶向基因修饰的效率的方法和组合物
ES2879373T3 (es) 2014-03-18 2021-11-22 Sangamo Therapeutics Inc Métodos y composiciones para la regulación de la expresión de proteínas de dedo de zinc
AU2015236033B2 (en) 2014-03-26 2018-06-07 University Of Maryland, College Park Targeted genome editing in zygotes of domestic large animals
GB201406968D0 (en) 2014-04-17 2014-06-04 Green Biologics Ltd Deletion mutants
KR101823661B1 (ko) 2014-04-24 2018-01-30 기초과학연구원 마이크로 상동 기반의 유전자 녹아웃을 위한 뉴클레아제 표적 서열을 확인하는 방법
GB201407852D0 (en) 2014-05-02 2014-06-18 Iontas Ltd Preparation of libraries od protein variants expressed in eukaryotic cells and use for selecting binding molecules
WO2015173436A1 (en) 2014-05-16 2015-11-19 Vrije Universiteit Brussel Genetic correction of myotonic dystrophy type 1
EP3149169A1 (en) 2014-05-30 2017-04-05 The Board of Trustees of the Leland Stanford Junior University Compositions and methods of delivering treatments for latent viral infections
KR102374379B1 (ko) 2014-06-06 2022-03-17 리제너론 파마슈티칼스 인코포레이티드 표적화된 좌를 변형시키는 방법 및 조성물
ES2788426T3 (es) 2014-06-16 2020-10-21 Univ Johns Hopkins Composiciones y métodos para la expresión de ARNs de guía de CRISPR utilizando el promotor de H1
CA3172866A1 (en) 2014-06-26 2015-12-30 Regeneron Pharamaceuticals, Inc. Methods and compositions for targeted genetic modifications and methods of use
US10738278B2 (en) 2014-07-15 2020-08-11 Juno Therapeutics, Inc. Engineered cells for adoptive cell therapy
US9944933B2 (en) 2014-07-17 2018-04-17 Georgia Tech Research Corporation Aptamer-guided gene targeting
EP3193944B1 (en) 2014-07-17 2021-04-07 University of Pittsburgh - Of the Commonwealth System of Higher Education Methods of treating cells containing fusion genes
JP6594955B2 (ja) 2014-08-27 2019-10-23 ニユー・イングランド・バイオレイブス・インコーポレイテツド シントン形成
US9970030B2 (en) 2014-08-27 2018-05-15 Caribou Biosciences, Inc. Methods for increasing CAS9-mediated engineering efficiency
EP3188763B1 (en) 2014-09-02 2020-05-13 The Regents of The University of California Methods and compositions for rna-directed target dna modification
AU2015311706A1 (en) 2014-09-07 2017-02-02 Selecta Biosciences, Inc. Methods and compositions for attenuating gene therapy anti-viral transfer vector immune responses
WO2016049024A2 (en) 2014-09-24 2016-03-31 The Broad Institute Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for modeling competition of multiple cancer mutations in vivo
WO2016049163A2 (en) 2014-09-24 2016-03-31 The Broad Institute Inc. Use and production of chd8+/- transgenic animals with behavioral phenotypes characteristic of autism spectrum disorder
WO2016049258A2 (en) 2014-09-25 2016-03-31 The Broad Institute Inc. Functional screening with optimized functional crispr-cas systems
CN107002098A (zh) 2014-09-29 2017-08-01 杰克逊实验室 通过电穿孔高效率、高通量产生遗传修饰哺乳动物
AU2015324935B2 (en) 2014-10-01 2021-04-08 The General Hospital Corporation Methods for increasing efficiency of nuclease-induced homology-directed repair
CA2963693A1 (en) 2014-10-10 2016-04-14 Editas Medicine, Inc. Compositions and methods for promoting homology directed repair
WO2016061073A1 (en) 2014-10-14 2016-04-21 Memorial Sloan-Kettering Cancer Center Composition and method for in vivo engineering of chromosomal rearrangements
EP3561052A1 (en) 2014-10-15 2019-10-30 Regeneron Pharmaceuticals, Inc. Methods and compositions for generating or maintaining pluripotent cells
CN107208086A (zh) 2014-10-17 2017-09-26 霍华德休斯医学研究所 基因组探针
US10308947B2 (en) 2014-10-17 2019-06-04 The Penn State Research Foundation Methods and compositions for multiplex RNA guided genome editing and other RNA technologies
WO2016065364A1 (en) 2014-10-24 2016-04-28 Life Technologies Corporation Compositions and methods for enhancing homologous recombination
EP3215623A4 (en) 2014-11-06 2018-09-26 President and Fellows of Harvard College Cells lacking b2m surface expression and methods for allogeneic administration of such cells
WO2016073990A2 (en) 2014-11-07 2016-05-12 Editas Medicine, Inc. Methods for improving crispr/cas-mediated genome-editing
ES2731437T3 (es) 2014-11-21 2019-11-15 Regeneron Pharma Métodos y composiciones para la modificación genética dirigida mediante el uso de pares de ARN guías
JP2017535296A (ja) 2014-11-27 2017-11-30 ダンツィガー イノベイションズ リミテッドDanziger Innovations Ltd. ゲノム編集のための核酸構築物
WO2016089866A1 (en) 2014-12-01 2016-06-09 President And Fellows Of Harvard College Rna-guided systems for in vivo gene editing
WO2016094880A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Delivery, use and therapeutic applications of crispr systems and compositions for genome editing as to hematopoietic stem cells (hscs)
WO2016094872A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Dead guides for crispr transcription factors
WO2016094874A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Escorted and functionalized guides for crispr-cas systems
WO2016097751A1 (en) 2014-12-18 2016-06-23 The University Of Bath Method of cas9 mediated genome engineering
US11326184B2 (en) 2014-12-19 2022-05-10 Regeneron Pharmaceuticals, Inc. Methods and compositions for targeted genetic modification through single-step multiple targeting
US10190106B2 (en) 2014-12-22 2019-01-29 Univesity Of Massachusetts Cas9-DNA targeting unit chimeras
WO2016108926A1 (en) 2014-12-30 2016-07-07 The Broad Institute Inc. Crispr mediated in vivo modeling and genetic screening of tumor growth and metastasis
US20180155708A1 (en) 2015-01-08 2018-06-07 President And Fellows Of Harvard College Split Cas9 Proteins
EP3242938B1 (en) 2015-01-09 2020-01-08 Bio-Rad Laboratories, Inc. Detection of genome editing
US11208638B2 (en) 2015-01-12 2021-12-28 The Regents Of The University Of California Heterodimeric Cas9 and methods of use thereof
CN107429263A (zh) 2015-01-15 2017-12-01 斯坦福大学托管董事会 调控基因组编辑的方法
IL288263B (en) 2015-01-28 2022-07-01 Caribou Biosciences Inc Crispr hybrid dna/rna polynucleotides and methods of use
WO2016130697A1 (en) 2015-02-11 2016-08-18 Memorial Sloan Kettering Cancer Center Methods and kits for generating vectors that co-express multiple target molecules
EP3262172A2 (en) 2015-02-23 2018-01-03 Crispr Therapeutics AG Materials and methods for treatment of hemoglobinopathies
WO2016135559A2 (en) 2015-02-23 2016-09-01 Crispr Therapeutics Ag Materials and methods for treatment of human genetic diseases including hemoglobinopathies
WO2016138574A1 (en) 2015-03-02 2016-09-09 Sinai Health System Homologous recombination factors
GB201504223D0 (en) 2015-03-12 2015-04-29 Genome Res Ltd Biallelic genetic modification
EP3851530A1 (en) 2015-03-26 2021-07-21 Editas Medicine, Inc. Crispr/cas-mediated gene conversion
US9790490B2 (en) 2015-06-18 2017-10-17 The Broad Institute Inc. CRISPR enzymes and systems

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CA2908697A1 (en) 2014-10-23
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US20140310828A1 (en) 2014-10-16
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US20170204430A1 (en) 2017-07-20
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ES2888250T3 (es) 2022-01-03
HK1214625A1 (zh) 2016-07-29
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US10385359B2 (en) 2019-08-20
SI2986729T1 (sl) 2019-02-28
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US20210301301A1 (en) 2021-09-30
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KR20200136508A (ko) 2020-12-07
US20140309487A1 (en) 2014-10-16
PL3456831T3 (pl) 2021-12-06
AU2014253942A1 (en) 2015-11-12
JP6411463B2 (ja) 2018-10-24
SMT201800671T1 (it) 2019-01-11
NZ713343A (en) 2021-08-27
BR112015026197B1 (pt) 2022-12-06
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